Klotho as a potential biomarker and therapy for acute kidney injury

Hu, Ming‐Chang; Moe, Orson W.

doi:10.1038/nrneph.2012.92

Cited by 155 publications

(133 citation statements)

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“…16) Emerging experimental and clinical evidence indicates that during the progression of AKI from diverse etiologies, sklotho decreases significantly in the early phase. [17][18][19] Also, gene expression studies in AKI have clearly demonstrated rapid and significant down regulation of KL mRNA in the thick ascending limb of Henle's loop and the collecting ducts, with resultant decreased synthesis of klotho protein and secretion into the circulation. 20,21) CIN, as a distinct subtype of AKI, might share a similar kidney damage process.…”

Section: Discussionmentioning

confidence: 99%

A Nomogram to Predict Contrast Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention

Zhuang

et al. 2017

Int. Heart J.

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SummaryContrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury (AKI). Emerging evidence has revealed that soluble klotho (sklotho) could be a novel biomarker for early AKI diagnosis. The aims of this study were to assess the predictive role of sklotho for CIN and to develop a prediction nomogram in patients undergoing percutaneous coronary intervention (PCI). This study is registered on Clinicaltrials.gov (NCT 02650336).Patients aged 18 years or older undergoing planned PCI were prospectively recruited between May 2014 and July 2015. CIN was defined as an increase in serum creatinine of 0.5 mg/dL within 48-72 hours after the procedure. Plasma sklotho was measured by enzyme linked immunosorbent assay (ELISA). Stratified analysis, interaction test, covariate screening, and curve fitting were performed to explore the association between sklotho and CIN. A nomogram was then developed and validated using the bootstrapped technique.A total of 192 patients aged 54.75 ± 12.19 years were selected, 32 (16.7%) of whom were diagnosed with CIN. A logistic regression model indicated significant associations between CIN and sklotho, age > 75 years, diabetes, and the Mehran risk score. Saturation effects analysis detected a two-stage change between sklotho and CIN, with the inflection point was 477.4 pg/mL. The area under the ROC curve was 0.758 and the sensitivity and specificity of this point were 90.6% and 53.9%, respectively. A nomogram was developed for the prediction of CIN and showed a bootstrapped-corrected area under the curve value of 0.913. In addition, sklotho significantly increased the predictive value of the nomogram.A strong association between sklotho and CIN was identified in patients undergoing elective PCI. A lower level of sklotho would be well correlated with CIN. The nomogram with sklotho is a useful tool to predict CIN in patients who will undergo PCI. (Int Heart J 2017; 58: 191-196)

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Section: Discussionmentioning

confidence: 99%

A Nomogram to Predict Contrast Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention

Zhuang

et al. 2017

Int. Heart J.

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“…The latter is derived from either cleavage of Klotho from the cell membrane or alternative splicing. Several renoprotective (18)(19)(20) and vasculoprotective (21,22) effects have been ascribed to sKlotho. With the recent establishment of an ELISA (23), sKlotho may become another CKD-MBD biomarker.…”

Section: Introductionmentioning

confidence: 99%

Associations of FGF-23 and sKlotho with Cardiovascular Outcomes among Patients with CKD Stages 2–4

Seiler

Rogačev

Roth

et al. 2014

Clinical Journal of the American Society of Nephrology

132

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Background and objectives CKD-mineral and bone disorders (CKD-MBD) measures contribute to cardiovascular morbidity in patients with CKD. Among these, fibroblast growth factor (FGF)-23 and its coreceptor Klotho may exert direct effects on vascular and myocardial tissues. Klotho exists in a membrane-bound and a soluble form (sKlotho). Recent experimental evidence suggests sKlotho has vasculoprotective functions.Design, settings, participants, & measurements Traditional and novel CKD-MBD variables were measured among 444 patients with CKD stages 2-4 recruited between September 2008 and November 2012 into the ongoing CARE FOR HOMe study. Across tertiles of baseline sKlotho and FGF-23, the incidence of two distinct combined end points was analyzed: (1) the first occurrence of an atherosclerotic event or death from any cause and (2) the time until hospital admission for decompensated heart failure or death from any cause.Results Patients were followed for 2.6 (interquartile range, 1.4-3.6) years. sKlotho tertiles predicted neither atherosclerotic events/death (fully adjusted Cox regression analysis: hazard ratio [HR] for third versus first sKlotho tertile, 0.75 [95% confidence interval (95% CI), 0.43-1.30]; P=0.30) nor the occurrence of decompensated heart failure/death (HR for third versus first sKlotho tertile, 0.81 [95% CI, 0.39-1.66]; P=0.56). In contrast, patients in the highest FGF-23 tertile had higher risk for both end points in univariate analysis. Adjustment for kidney function attenuated the association between FGF-23 and atherosclerotic events/death (HR for third versus first FGF-23 tertile, 1.23 [95% CI, 0.58-2.61]; P=0.59), whereas the association between FGF-23 and decompensated heart failure/death remained significant after adjustment for confounders (HR for third versus first FGF-23 tertile, 4.51 [95% CI, 1.33-15.21]; P=0.02).Conclusions In this prospective observational study of limited sample size, sKlotho was not significantly related to cardiovascular outcomes. FGF-23 was significantly associated with future decompensated heart failure but not incident atherosclerotic events.

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“…5 TNF superfamily inflammatory cytokines, TGF-b1 or angiotensin II, decrease Klotho expression in cultured tubular cells. 2,3,7,8 Zhou et al 4 confirm a TNFindependent Klotho-lowering effect of TGF-b1 in cultured renal cells. Zhou et al 4 propose that TGF-b1 could be the culprit behind Klotho depletion in diseased kidneys.…”

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confidence: 99%

“…A key function of Klotho is to regulate phosphate metabolism by both being a necessary coreceptor for the phosphaturic hormone fibroblast growth factor-23 and directly inhibiting tubular phosphate reabsorption by the sodium-phosphate cotransporter NaPi2a. 2,3 In addition, a growing list of actions of soluble Klotho depend on its glycosidase activity or binding to cell membrane receptors and transporters and as reported by Zhou et al, 2,4 soluble ligands. Thus, Klotho regulates insulin/IGF-1, Wnt, and TGF-b1 signaling as well as renal outer medullary potassium channel (ROMK), transient receptor potential channel 5 (TRPC5), and TRPC6 availability.…”

mentioning

confidence: 99%

“…Thus, Klotho regulates insulin/IGF-1, Wnt, and TGF-b1 signaling as well as renal outer medullary potassium channel (ROMK), transient receptor potential channel 5 (TRPC5), and TRPC6 availability. 2 Loss of Klotho may contribute to the aging-like features of human CKD and progression of CKD. [5][6][7] The initial description of the mouse Klotho gene reported normal serum creatinine in mutant mice.…”

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confidence: 99%

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